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Papers by angelo angelo

Research paper thumbnail of Turning Brain into Blood: A Hematopoietic Fate Adopted by Adult Neural Stem Cells in Vivo

Research paper thumbnail of PCR-amplified microsatellites as markers in plant genetics

Plant Journal, Jan 1, 1993

In order to assess the feasibility of using microsatellites as markers in plant genetics, a surve... more In order to assess the feasibility of using microsatellites as markers in plant genetics, a survey of published DNA sequence data for presence, abundance and ubiquity in higher plants of all types of dinucleotide and trinucleotide repeats with a minimum number of 10 and 7 units, respectively, was conducted. This search revealed that such microsatellites are frequent and widely distributed; they were uncovered in 34 species, with a frequency of one every 50 kb. AT repeats were by far the most frequently observed class of dinucleotide microsatellites, whereas AC/TG repeats, which are common in animals, were observed only once. TAT repeats prevailed among trinucleotides. Polymerase chain reaction amplification of (AT)n and (TAT)n micro-satellites in soybean (Glycine max (L.) Merr.) revealed that they are highly polymorphic, as a consequence of length variation, somatically stable and inherited in a co-dominant Mendelian manner. The abundance and amount of information derived from such markers, together with the ease by which they can be identified, make them ideal markers for plant genetic linkage and physical mapping, population studies and varietal identification.

Research paper thumbnail of Nonsurgical Reconstruction of Thoracic Aortic Dissection by Stent–Graft Placement

New England Journal of Medicine, Jan 1, 1999

The treatment of thoracic aortic dissection is guided by prognostic and anatomical information. P... more The treatment of thoracic aortic dissection is guided by prognostic and anatomical information. Proximal dissection requires surgery, but the appropriate treatment of distal thoracic aortic dissection has not been determined, because surgery has failed to improve the prognosis. We prospectively evaluated the safety and efficacy of elective transluminal endovascular stent-graft insertion in 12 consecutive patients with descending (type B) aortic dissection and compared the results with surgery in 12 matched controls. In all 24 patients, aortic dissection was diagnosed by magnetic resonance angiography. In each group, the dissection involved the aortic arch in 3 patients and the descending thoracic aorta in all 12 patients. With the patient under general anesthesia, either surgical resection was undertaken or a custom-designed endovascular stent-graft was placed by unilateral arteriotomy. Stent-graft placement resulted in no morbidity or mortality, whereas surgery for type B dissection was associated with four deaths (33 percent, P=0.09) and five serious adverse events (42 percent, P=0.04) within 12 months. Transluminal placement of the stent-graft prosthesis was successful in all patients, with no leakage; full expansion of the stents was ensured by balloon inflation at 2 to 3 atm. Sealing of the entry tear was monitored during the procedure by transesophageal ultrasonography and angiography, and thrombosis of the false lumen was confirmed in all 12 patients after a mean of three months by magnetic resonance imaging. There were no deaths or instances of paraplegia, stroke, embolization, side-branch occlusion, or infection in the stent-graft group; nine patients had postimplantation syndrome, with transient elevation of C-reactive protein levels and body temperature plus mild leukocytosis. All the patients who received stent-grafts recovered, as did seven patients who underwent surgery for type B dissection (58 percent) (P=0.04). These preliminary observations suggest that elective, nonsurgical insertion of an endovascular stent-graft is safe and efficacious in selected patients who have thoracic aortic dissection and for whom surgery is indicated. Endoluminal repair may be useful for interventional reconstruction of thoracic aortic dissection.

Research paper thumbnail of Intermittent Cyclical Etidronate Treatment of Postmenopausal Osteoporosis

New England Journal of Medicine, Jan 1, 1990

to one year of treatment with estradiol and norethistcrone acetate. nandrolone decanoate. or calc... more to one year of treatment with estradiol and norethistcrone acetate. nandrolone decanoate. or calcitonin. all drugs with a beneficial effect on bone. All three trials were double-blind and placebo-controlled; I04 women (87%) completed the study. We measured the total serum concentration of l.25-dihydroxyvitamin D (l.25(OH),D and vitamin D-binding protein. and estimated the free 1.25(OH),D) index and the '24-hydroxylase activity' initially. and at 6 and 12 months. Furthermore. the 24-h &nary excretions of calcium, phosphate. and adenosine 3'-S'-cyclic mDnophosphate were assessed initially and at I2 months. The serum concentration of vitamin Dbindmg protein and 1.25(OH),D increased transiently during estradiol and norethisterone acetate treatment and vitamin D-binding protein decreased transiently during nandrolone decanoate treatment. None of the other parameters were significantly affected by any of the three treatments. The risk of type II errors was below IO per cent for all vitamin D measurements. We conclude that the vitamin D metabolites are unlikely to be of major importance for the mechanism by which these drugs exert their positive skeletal eNects.

Research paper thumbnail of cDNA sequence of human apolipoprotein(a) is homologous to plasminogen

Research paper thumbnail of Diffuse large B-cell lymphoma outcome prediction by gene- expression profiling and supervised machine learning

Diffuse large B-cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is curable ... more Diffuse large B-cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is curable in less than 50% of patients. Prognostic models based on pre-treatment characteristics, such as the International Prognostic Index (IPI), are currently used to predict outcome in DLBCL. However, clinical outcome models identify neither the molecular basis of clinical heterogeneity, nor specific therapeutic targets. We analyzed the expression of 6,817 genes in diagnostic tumor specimens from DLBCL patients who received cyclophosphamide, adriamycin, vincristine and prednisone (CHOP)-based chemotherapy, and applied a supervised learning prediction method to identify cured versus fatal or refractory disease. The algorithm classified two categories of patients with very different five-year overall survival rates (70% versus 12%). The model also effectively delineated patients within specific IPI risk categories who were likely to be cured or to die of their disease. Genes implicated in DLBCL outcome included some that regulate responses to B-cell-receptor signaling, critical serine/threonine phosphorylation pathways and apoptosis. Our data indicate that supervised learning classification techniques can predict outcome in DLBCL and identify rational targets for intervention.

Research paper thumbnail of Prediction of central nervous system embryonal tumour outcome based on gene expression

Research paper thumbnail of Multiclass cancer diagnosis using tumor gene expression signatures

Proceedings of The National Academy of Sciences, Jan 1, 2001

The optimal treatment of patients with cancer depends on establishing accurate diagnoses by using... more The optimal treatment of patients with cancer depends on establishing accurate diagnoses by using a complex combination of clinical and histopathological data. In some instances, this task is difficult or impossible because of atypical clinical presentation or histopathology. To determine whether the diagnosis of multiple common adult malignancies could be achieved purely by molecular classification, we subjected 218 tumor samples, spanning 14 common tumor types, and 90 normal tissue samples to oligonucleotide microarray gene expression analysis. The expression levels of 16,063 genes and expressed sequence tags were used to evaluate the accuracy of a multiclass classifier based on a support vector machine algorithm. Overall classification accuracy was 78%, far exceeding the accuracy of random classification (9%). Poorly differentiated cancers resulted in low-confidence predictions and could not be accurately classified according to their tissue of origin, indicating that they are molecularly distinct entities with dramatically different gene expression patterns compared with their well differentiated counterparts. Taken together, these results demonstrate the feasibility of accurate, multiclass molecular cancer classification and suggest a strategy for future clinical implementation of molecular cancer diagnostics.

Research paper thumbnail of Minimizing multimodal functions of continuous variables with the “simulated annealing” algorithm

ACM Transactions on Mathematical Software, Jan 1, 1987

A. CORANA, M. MARCHESI, C. MARTINI, and S. RIDELLA lstituto per i Circuiti Elettronici-C.N.R.

Research paper thumbnail of Immunochemical quantitation of antigens by single radial immunodiffusion

Immunochemistry, Jan 1, 1965

When an unknown amount of antigen is allowed to diffuse radially from a well in a uniformly thin ... more When an unknown amount of antigen is allowed to diffuse radially from a well in a uniformly thin layer of antibody-containing agar for a sufficient time to allow all antigen to combine, the final area reached by the precipitate is directly proportional to the amount of antigen employed, and inversely proportional to the concentration of antibody. It is also shown that the temperature at which the plates are incubated has no perceptible influence upon the results. By standardizing the technical conditions of the experiment it is possible to use this principle for the immunochemical determination of antigens. In the experimental albumin-antialbumin system here described, the lower limit of the method was found to correspond to 0·0025 μg of antigen, and to an antigen concentrations of 1·25 μg per ml. The standard deviation of the antigen determinations was less than 2 per cent of the mean.

Research paper thumbnail of Turning Brain into Blood: A Hematopoietic Fate Adopted by Adult Neural Stem Cells in Vivo

Research paper thumbnail of PCR-amplified microsatellites as markers in plant genetics

Plant Journal, Jan 1, 1993

In order to assess the feasibility of using microsatellites as markers in plant genetics, a surve... more In order to assess the feasibility of using microsatellites as markers in plant genetics, a survey of published DNA sequence data for presence, abundance and ubiquity in higher plants of all types of dinucleotide and trinucleotide repeats with a minimum number of 10 and 7 units, respectively, was conducted. This search revealed that such microsatellites are frequent and widely distributed; they were uncovered in 34 species, with a frequency of one every 50 kb. AT repeats were by far the most frequently observed class of dinucleotide microsatellites, whereas AC/TG repeats, which are common in animals, were observed only once. TAT repeats prevailed among trinucleotides. Polymerase chain reaction amplification of (AT)n and (TAT)n micro-satellites in soybean (Glycine max (L.) Merr.) revealed that they are highly polymorphic, as a consequence of length variation, somatically stable and inherited in a co-dominant Mendelian manner. The abundance and amount of information derived from such markers, together with the ease by which they can be identified, make them ideal markers for plant genetic linkage and physical mapping, population studies and varietal identification.

Research paper thumbnail of Nonsurgical Reconstruction of Thoracic Aortic Dissection by Stent–Graft Placement

New England Journal of Medicine, Jan 1, 1999

The treatment of thoracic aortic dissection is guided by prognostic and anatomical information. P... more The treatment of thoracic aortic dissection is guided by prognostic and anatomical information. Proximal dissection requires surgery, but the appropriate treatment of distal thoracic aortic dissection has not been determined, because surgery has failed to improve the prognosis. We prospectively evaluated the safety and efficacy of elective transluminal endovascular stent-graft insertion in 12 consecutive patients with descending (type B) aortic dissection and compared the results with surgery in 12 matched controls. In all 24 patients, aortic dissection was diagnosed by magnetic resonance angiography. In each group, the dissection involved the aortic arch in 3 patients and the descending thoracic aorta in all 12 patients. With the patient under general anesthesia, either surgical resection was undertaken or a custom-designed endovascular stent-graft was placed by unilateral arteriotomy. Stent-graft placement resulted in no morbidity or mortality, whereas surgery for type B dissection was associated with four deaths (33 percent, P=0.09) and five serious adverse events (42 percent, P=0.04) within 12 months. Transluminal placement of the stent-graft prosthesis was successful in all patients, with no leakage; full expansion of the stents was ensured by balloon inflation at 2 to 3 atm. Sealing of the entry tear was monitored during the procedure by transesophageal ultrasonography and angiography, and thrombosis of the false lumen was confirmed in all 12 patients after a mean of three months by magnetic resonance imaging. There were no deaths or instances of paraplegia, stroke, embolization, side-branch occlusion, or infection in the stent-graft group; nine patients had postimplantation syndrome, with transient elevation of C-reactive protein levels and body temperature plus mild leukocytosis. All the patients who received stent-grafts recovered, as did seven patients who underwent surgery for type B dissection (58 percent) (P=0.04). These preliminary observations suggest that elective, nonsurgical insertion of an endovascular stent-graft is safe and efficacious in selected patients who have thoracic aortic dissection and for whom surgery is indicated. Endoluminal repair may be useful for interventional reconstruction of thoracic aortic dissection.

Research paper thumbnail of Intermittent Cyclical Etidronate Treatment of Postmenopausal Osteoporosis

New England Journal of Medicine, Jan 1, 1990

to one year of treatment with estradiol and norethistcrone acetate. nandrolone decanoate. or calc... more to one year of treatment with estradiol and norethistcrone acetate. nandrolone decanoate. or calcitonin. all drugs with a beneficial effect on bone. All three trials were double-blind and placebo-controlled; I04 women (87%) completed the study. We measured the total serum concentration of l.25-dihydroxyvitamin D (l.25(OH),D and vitamin D-binding protein. and estimated the free 1.25(OH),D) index and the '24-hydroxylase activity' initially. and at 6 and 12 months. Furthermore. the 24-h &nary excretions of calcium, phosphate. and adenosine 3'-S'-cyclic mDnophosphate were assessed initially and at I2 months. The serum concentration of vitamin Dbindmg protein and 1.25(OH),D increased transiently during estradiol and norethisterone acetate treatment and vitamin D-binding protein decreased transiently during nandrolone decanoate treatment. None of the other parameters were significantly affected by any of the three treatments. The risk of type II errors was below IO per cent for all vitamin D measurements. We conclude that the vitamin D metabolites are unlikely to be of major importance for the mechanism by which these drugs exert their positive skeletal eNects.

Research paper thumbnail of cDNA sequence of human apolipoprotein(a) is homologous to plasminogen

Research paper thumbnail of Diffuse large B-cell lymphoma outcome prediction by gene- expression profiling and supervised machine learning

Diffuse large B-cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is curable ... more Diffuse large B-cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is curable in less than 50% of patients. Prognostic models based on pre-treatment characteristics, such as the International Prognostic Index (IPI), are currently used to predict outcome in DLBCL. However, clinical outcome models identify neither the molecular basis of clinical heterogeneity, nor specific therapeutic targets. We analyzed the expression of 6,817 genes in diagnostic tumor specimens from DLBCL patients who received cyclophosphamide, adriamycin, vincristine and prednisone (CHOP)-based chemotherapy, and applied a supervised learning prediction method to identify cured versus fatal or refractory disease. The algorithm classified two categories of patients with very different five-year overall survival rates (70% versus 12%). The model also effectively delineated patients within specific IPI risk categories who were likely to be cured or to die of their disease. Genes implicated in DLBCL outcome included some that regulate responses to B-cell-receptor signaling, critical serine/threonine phosphorylation pathways and apoptosis. Our data indicate that supervised learning classification techniques can predict outcome in DLBCL and identify rational targets for intervention.

Research paper thumbnail of Prediction of central nervous system embryonal tumour outcome based on gene expression

Research paper thumbnail of Multiclass cancer diagnosis using tumor gene expression signatures

Proceedings of The National Academy of Sciences, Jan 1, 2001

The optimal treatment of patients with cancer depends on establishing accurate diagnoses by using... more The optimal treatment of patients with cancer depends on establishing accurate diagnoses by using a complex combination of clinical and histopathological data. In some instances, this task is difficult or impossible because of atypical clinical presentation or histopathology. To determine whether the diagnosis of multiple common adult malignancies could be achieved purely by molecular classification, we subjected 218 tumor samples, spanning 14 common tumor types, and 90 normal tissue samples to oligonucleotide microarray gene expression analysis. The expression levels of 16,063 genes and expressed sequence tags were used to evaluate the accuracy of a multiclass classifier based on a support vector machine algorithm. Overall classification accuracy was 78%, far exceeding the accuracy of random classification (9%). Poorly differentiated cancers resulted in low-confidence predictions and could not be accurately classified according to their tissue of origin, indicating that they are molecularly distinct entities with dramatically different gene expression patterns compared with their well differentiated counterparts. Taken together, these results demonstrate the feasibility of accurate, multiclass molecular cancer classification and suggest a strategy for future clinical implementation of molecular cancer diagnostics.

Research paper thumbnail of Minimizing multimodal functions of continuous variables with the “simulated annealing” algorithm

ACM Transactions on Mathematical Software, Jan 1, 1987

A. CORANA, M. MARCHESI, C. MARTINI, and S. RIDELLA lstituto per i Circuiti Elettronici-C.N.R.

Research paper thumbnail of Immunochemical quantitation of antigens by single radial immunodiffusion

Immunochemistry, Jan 1, 1965

When an unknown amount of antigen is allowed to diffuse radially from a well in a uniformly thin ... more When an unknown amount of antigen is allowed to diffuse radially from a well in a uniformly thin layer of antibody-containing agar for a sufficient time to allow all antigen to combine, the final area reached by the precipitate is directly proportional to the amount of antigen employed, and inversely proportional to the concentration of antibody. It is also shown that the temperature at which the plates are incubated has no perceptible influence upon the results. By standardizing the technical conditions of the experiment it is possible to use this principle for the immunochemical determination of antigens. In the experimental albumin-antialbumin system here described, the lower limit of the method was found to correspond to 0·0025 μg of antigen, and to an antigen concentrations of 1·25 μg per ml. The standard deviation of the antigen determinations was less than 2 per cent of the mean.